The laboratory has found significant differences in plasma protein composition, by analysis with high resolution two dimensional protein electrophoresis, between monozygotic twins discordant for schizophrenia. Schizophrenia is known to be associated with hereditary and extra- hereditary risk factors. We used sets of twins that were genetically identical to gain insight into extra-hereditary factors in schizophrenia. We found a greater variation in the plasma protein composition between twins discordant for schizophrenia than between normal monozygotic twins and monozygotic twins concordant for schizophrenia. Some of these differences were reflected in plasma haptoglobin concentrations suggesting a systemic alteration in metabolism in schizophrenia and/or a systemic inflammatory abnormality. In addition, the laboratory has found significant differences in the distribution of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) of individuals with Alzheimer's disease. The Apo-E4 genotype has been associated with an increased risk of developing Alzheimer's disease. We have shown this also true of the apo-E4 phenotype. We have also found that while there are equivalent amounts of apo-E3 and apo-E4 in the in the CSF of normal individuals there is a reduced amount of apoE3 in the CSF of Alzheimer's disease patients. To facilitate our analysis of protein alterations in disease states, the Laboratory has developed a relational database to facilitate quantitative and qualitative comparisons of proteins in human body fluids in normal and disease states. Currently, most clinicians evaluate only a few specific proteins in a body fluid such as plasma when they suspect that a patient has a disease. Now, however, high-resolution two dimensional protein electrophoresis allows the simultaneous evaluation of 1,500 to 3,000 proteins in complex solutions, such as the body fluids. This and other high resolution methods have encouraged us to collect the clinical data for the body fluid proteins into an easily accessed database. This database will provide a linkage between the disease-associated protein alterations and images of the appropriate proteins on high-resolution electrophoretic gels of the body fluids.